The present invention relates to coated articles such as biomedical articles, especially contact lenses, which are at least partly coated with a hydrophilic polymer, and to a process for the manufacture of said coated articles.
A variety of different types of processes for preparing hydrophilic polymeric coatings on an xe2x80x9cinertxe2x80x9d hydrophobic substrate have been disclosed in the prior art. For example, WO 99/57581 discloses to first of all provide the article surface with covalently bound photoinitiator molecules, coating the modified surface with a layer of a polymerizable macromonomer and then subjecting it to a heat or radiation treatment whereby the macromonomer is graft polymerized thus forming the novel article surface. The covalent binding of the photoinitiator molecules to the article surface is created by first subjecting the article surface to a plasma treatment thereby providing the surface with functional groups, and then reacting said functional groups with coreactive groups of a functional photoinitiator.
A plasma treatment requires a considerable investment in equipment and is furthermore difficult to be integrated in an automated production process. For example, a plasma treatment requires that the article to be treated is dry before exposure to the plasma. Thus, a polymeric article such as a contact lens that is wet from prior hydration or extraction must be dried previously, thereby adding time in the overall lens production process as well as imposing added costs of obtaining a drying equipment.
Therefore, it would be highly desirable to modify the surface functionalization step of the process disclosed in WO 99/57581 such that the plasma treatment is avoided and replaced by a technique which is easy to perform with standard equipment and which is thus more feasible for an automated production process.
Surprisingly, it has now been found, that hydrophobic articles may be readily functionalized by adding at least one polyelectrolyte or preferably a bilayer of functional polyelectrolytes to the article surface. The functional groups of the polyelectrolytes that are adsorbed and/or heteropolarly bound on the surface then may be used for the covalent attachment of polymerization initiators which in turn may initiate the graft polymerization of suitable hydrophilic monomers or macromonomers onto the article surface.
The present invention therefore in one aspect relates to a composite material comprising
(a) an inorganic or organic bulk material having attached to its surface a polyionic material that comprises covalently bound initiator moieties for radical polymerization; and
(b) a hydrophilic surface coating obtainable by applying one or more different ethylenically unsaturated hydrophilic monomers or macromonomers to the bulk material surface provided with the initiator radicals and polymerizing said monomers or macromonomers.
The bulk material underlying the composite materials of the invention is preferably a material that is devoid of ionic groups such as cationic or anionic groups. Accordingly, the surface of the preferred bulk materials is also devoid of ionic groups such as carboxy, sulfo, amino and the like groups and is thus substantially free from ionic charges.
Examples of suitable bulk materials are quartz, ceramics, glasses, silicate minerals, silica gels, metals, metal oxides, carbon materials such as graphite or glassy carbon, natural or synthetic organic polymers, or laminates, composites or blends of said materials, in particular natural or synthetic organic polymers or modified biopolymers which are known in large number. Some examples of polymers are polyaddition and polycondensation polymers (polyurethanes, epoxy resins, polyethers, polyesters, polyamides and polyimides); vinyl polymers (polyacrylates, polymethacrylates, polyacrylamides, polymethacrylamides, polystyrene, polyethylene and halogenated derivatives thereof, polyvinyl acetate and polyacrylonitrile); or elastomers (silicones, polybutadiene and polyisoprene).
A preferred group of materials to be coated are those being conventionally used for the manufacture of biomedical devices, e.g. contact lenses, in particular contact lenses for extended wear, which are not hydrophilic per se. Such materials are known to the skilled artisan and may comprise for example polysiloxanes, perfluoroalkyl polyethers, fluorinated poly(meth)acrylates or equivalent fluorinated polymers derived e.g. from other polymerizable carboxylic acids, polyalkyl (meth)acrylates or equivalent alkylester polymers derived from other polymerizable carboxylic acids, or fluorinated polyolefines, such as fluorinated ethylene or propylene, for example tetrafluoroethylene, preferably in combination with specific dioxols, such as perfluoro-2,2-dimethyl-1,3-dioxol. Examples of suitable bulk materials are e.g. Lotrafilcon A, Neofocon, Pasifocon, Telefocon, Silafocon, Fluorsilfocon, Paflufocon, Silafocon, Elastofilcon, Fluorofocon or Teflon AF materials, such as Teflon AF 1600 or Teflon AF 2400 which are copolymers of about 63 to 73 mol % of perfluoro-2,2-dimethyl-1,3-dioxol and about 37 to 27 mol % of tetrafluoroethylene, or of about 80 to 90 mol % of perfluoro-2,2-dimethyl-1,3-dioxol and about 20 to 10 mol % of tetrafluoroethylene.
Another group of preferred materials to be coated are amphiphilic segmented copolymers comprising at least one hydrophobic segment and at least one hydrophilic segment which are linked through a bond or a bridge member. Examples are silicone hydrogels, for example those disclosed in PCT applications WO 96/31792 and WO 97/49740 which are herewith incorporated by reference.
A particular preferred group of bulk materials comprises organic polymers selected from polyacrylates, polymethacrylates, polyacrylamides, poly(N,N-dimethylacrylamides), polymethacrylamides, polyvinyl acetates, polysiloxanes, perfluoroalkyl polyethers, fluorinated polyacrylates or -methacrylates and amphiphilic segmented copolymers comprising at least one hydrophobic segment, for example a polysiloxane or perfluoroalkyl polyether segment or a mixed polysiloxane/perfluoroalkyl polyether segment, and at least one hydrophilic segment, for example a polyoxazoline, poly(2-hydroxyethylmethacrylate), polyacrylamide, poly(N,N-dimethylacrylamide), polyvinylpyrrolidone polyacrylic or polymethacrylic acid segment or a copolymeric mixture of two or more of the underlying monomers.
The material to be coated may also be any blood-contacting material conventionally used for the manufacture of renal dialysis membranes, blood storage bags, pacemaker leads or vascular grafts. For example, the material to be modified on its surface may be a polyurethane, polydimethylsiloxane, polytetrafluoroethylene, polyvinylchloride, Dacron(trademark) or Silastic(trademark) type polymer, or a composite made therefrom.
Moreover, the material to be coated may also be an inorganic or metallic base material without suitable reactive groups, e.g. ceramic, quartz, or metals, such as silicon or gold, or other polymeric or non-polymeric substrates. E.g. for implantable biomedical applications, ceramics are very useful. In addition, e.g. for biosensor purposes, hydrophilically coated base materials are expected to reduce nonspecific binding effects if the structure of the coating is well controlled. Biosensors may require a specific carbohydrate coating on gold, quartz, or other non-polymeric substrates.
The form of the material to be coated may vary within wide limits. Examples are particles, granules, capsules, fibres, tubes, films or membranes, preferably moldings of all kinds such as ophthalmic moldings, for example intraocular lenses, artificial cornea or in particular contact lenses.
The polyionic material being attached to the bulk material surface may consist of one single ionic polymer, for example of a polyanionic or polycationic material as described below.
Preferably, the polyionic material includes at least one bilayer, the bilayer comprising a first ionic polymer and a second ionic polymer having charges opposite of the charges of the first ionic polymer.
A suitable bilayer on the bulk material comprises a first and second ionic polymer having opposite charges, wherein xe2x80x9cfirst ionic polymerxe2x80x9d indicates the polymer that is first of all applied to the article surface, and xe2x80x9csecond ionic polymerxe2x80x9d indicates the polymer that is applied to the article surface after it has already been modified with the first ionic polymer. The bulk material may comprise one or more than one bilayers, for example from 1 to 25 bilayers containing the same or different ionic polymers in each case, preferably from 1 to 20 bilayers, more preferably 1 to 10 bilayers, even more prefereably 1 to 5 bilayers and in particular just one bilayer.
The first ionic polymer may be cationic or anionic, preferably anionic. A suitable anionic polymer is, for example, a synthetic polymer, biopolymer or modified biopolymer comprising carboxy, sulfo, sulfato, phosphono or phosphato groups or a mixture thereof, or a salt thereof, for example a biomedical acceptable salt and especially an ophthalmically acceptable salt thereof. Anionic polymers comprising carboxy groups or a suitable salt thereof are preferred.
Examples of synthetic anionic polymers are: a linear polyacrylic acid (PAA), a branched polyacrylic acid, for example a Carbophile or Carbopol(copyright) type from Goodrich Corp., a polymethacrylic acid (PMA), a polyacrylic acid or polymethacrylic acid copolymer, for example a copolymer of acrylic or methacrylic acid and a further vinylmonomer, for example acrylamide, N,N-dimethyl acrylamide or N-vinylpyrrolidone, a maleic or fumaric acid copolymer, a poly(styrenesulfonic acid) (PSS), a polyamido acid, for example a carboxy-terminated polymer of a diamine and a di- or polycarboxylic acid, for example carboxy-terminated Starburst(trademark) PAMAM dendrimers (Aldrich), a poly(2-acrylamido-2-methylpropanesulfonic acid) (poly-(AMPS)), or an alkylene polyphosphate, alkylene polyphosphonate, carbohydrate polyphosphate or carbohydrate polyphosphonate, for example a teichoic acid.
Examples of anionic biopolymers or modified biopolymers are: hyaluronic acid, glycosaminoglycanes such as heparin or chondroitin sulfate, fucoidan, poly-aspartic acid, poly-glutamic acid, carboxymethyl cellulose, carboxymethyl dextranes, alginates, pectins, gellan, carboxyalkyl chitins, carboxymethyl chitosans, sulfated polysaccharides.
A preferred anionic polymer is a linear or branched polyacrylic acid or an acrylic acid copolymer. A more preferred anionic polymer is a linear or branched polyacrylic acid. A branched polyacrylic acid in this context is to be understood as meaning a polyacrylic acid obtainable by polymerizing acrylic acid in the presence of suitable (minor) amounts of a di- or polyvinyl compound.
A suitable cationic polymer as part of the bilayer is, for example, a synthetic polymer, biopolymer or modified biopolymer comprising primary, secondary or tertiary amino groups or a suitable salt thereof, preferably an ophthalmically acceptable salt thereof, for example a hydrohalogenide such as a hydrochloride thereof, in the backbone or as substituents. Cationic polymers comprising primary or secondary amino groups or a salt thereof are preferred.
Examples of synthetic cationic polymers are:
(i) a polyallylamine (PAH) homo- or copolymer, optionally comprising modifier units;
(ii) a polyethyleneimine (PEI);
(iii) a polyvinylamine homo- or copolymer, optionally comprising modifier units;
(iv) a poly(vinylbenzyl-tri-C1-C4-alkylammonium salt), for example a poly(vinylbenzyl-tri-methyl ammoniumchloride);
(v) a polymer of an aliphatic or araliphatic dihalide and an aliphatic N,N,Nxe2x80x2,Nxe2x80x2-tetra-C1-C4-alkyl-alkylenediamine, for example a polymer of (a) propylene-1,3-dichloride or -dibromide or p-xylylene dichloride or dibromide and (b) N,N,Nxe2x80x2,Nxe2x80x2-tetramethyl-1,4-tetramethylene diamine;
(vi) a poly(vinylpyridin) or poly(vinylpyridinium salt) homo- or copolymer;
(vii) a poly (N,N-diallyl-N,N-di-C1-C4-alkyl-ammoniumhalide) comprising units of formula 
wherein R2 and R2xe2x80x2 are each independently C1-C4-alkyl, in particular methyl, and Anxe2x88x92 is a, for example, a halide anion such as the chloride anion;
(viii) a homo- or copolymer of a quaternized di-C1-C4-alkyl-aminoethyl acrylate or methacrylate, for example a poly(2-hydroxy-3-methacryloylpropyltri-C1-C2-alkylammonium salt) homopolymer such as a a poly(2-hydroxy-3-methacryloylpropyltri-methylammonium chloride), or a quaternized poly(2-dimethylaminoethyl methacrylate or a quaternized poly(vinylpyrrolidone-co-2-dimethylaminoethyl methacrylate);
(ix) POLYQUAD(copyright) as disclosed in EP-A-456,467; or
(x) a polyaminoamide (PAMAM), for example a linear PAMAM or a PAMAM dendrimer such as a amino-terminated Starbust(trademark) PAMAM dendrimer (Aldrich).
The above mentioned polymers comprise in each case the free amine, a suitable salt thereof, for example a biomedically acceptable salt or in particular an ophthalmically acceptable salt thereof, as well as any quaternized form, if not specified otherwise.
Suitable comonomers optionally incorporated in the polymers according to (i), (iii), (vi) or (viii) above are, for example, acrylamide, methacrylamide, N,N-dimethyl acrylamide, N-vinylpyrrolidone and the like.
Suitable modifier units of the polyallylamine (i) are, for example, of formula 
wherein L is C2-C6-alkyl which is substituted by two or more same or different substituents selected from the group consisting of hydroxy, C2-C5-alkanoyloxy and C2-C5-alkylaminocarbonyloxy.
L is preferably linear C3-C6-alkyl, more preferably linear C4-C5-alkyl, and most preferably n-pentyl which is in each case substituted as defined above.
Suitable substituents of the alkyl radical L are xe2x80x94OH, a radical xe2x80x94Oxe2x80x94C(O)xe2x80x94R29 and/or a radical xe2x80x94Oxe2x80x94C(O)xe2x80x94NHxe2x80x94R29, wherein R29 and R29xe2x80x2 are each independently of the other C1-C4-alkyl, preferably methyl, ethyl or n- or iso-propyl, and more preferably methyl or ethyl.
Preferred substituents of the alkyl radical L are hydroxy, acetyloxy, propionyloxy, methyl-aminocarbonyloxy or ethylaminocarbonyloxy, especially hydroxy, acetyloxy or propionyloxy and in particular hydroxy.
A preferred embodiment relates to polyallyl amines comprising units of the above formula (5), wherein L is a radical of formula 
wherein g is 1, 2, 3, 4 or 5, preferably 3 or 4 and in particular 4, each R* is independently hydrogen or a radical xe2x80x94C(O)xe2x80x94R29 or xe2x80x94C(O)xe2x80x94NHxe2x80x94R29xe2x80x2, and for R29 and R29xe2x80x2 the above meanings and preferences apply. L is even more preferred a radical of the above formula (6) wherein g is 3 or 4, in particular 4, and each group xe2x80x94OR* independently is hydroxy or hydroxy which is partly or completely acetylated, in particular hydroxy. Particular preferred radicals L are 1,2,3,4,5-pentahydroxy-n-pentyl or 1,2,3,4,5-pentahydroxy-n-pentyl wherein the hydroxy groups are partly or completely acetylated.
The modified polyallylamines of the invention are derivatives of a polyallyl amine that, based on the number of amino groups of the polyallyl amine, comprise from about 1 to 99%, preferably from 10 to 80%, more preferably, from 15 to 75%, even more preferably 20 to 70% and in particular 40 to 60%, of units of formula (5).
The term units of formula (5) or of another formula number below is always to be understood as encompassing one or more different species failing under the respective formula. Preferably the term means one single species. In addition, the polyallylamine may contain further modifier units, for example those disclosed in EP-A-1002807, formula (2a)-(2d).
A preferred polyallylamine according to the invention is a polyallylamine without modifier units or a polyallylamine having from 10 to 80% of units of the above formula (5) based on the number of amino groups of the polyallyl amine. A particular preferred polyallylamine according to the invention is a polyallylamine without modifier units or a polyallylamine having from 15 to 75%, based on the number of amino groups of the polyallyl amine, of units of the above formula (5) wherein L is 1,2,3,4,5-pentahydroxy-n-pentyl.
Suitable modifier units of the polyvinylamine (iii) are, for example, of formula 
wherein for L the above-given meanings and preferences apply.
A suitable polyvinylamine copolymer is, for example, a copolymer comprising vinylamine units and units derived from another hydrophilic comonomer, for example from acrylamide, N,N-dimethyl acrylamide, N-vinylpyrrolidone or the like.
Examples of cationic biopolymers or modified biopolymers are: basic peptides, proteins or glucoproteins, for example a poly-s-lysine, albumin or collagen, aminoalkylated polysaccharides, for example a chitosan, aminodextranes.
A preferred cationic polymer forming the bilayer that is attached to the bulk material is a polyallylamine homopolymer; a polyallylamine comprising modifier units of the above formula (1); a polyvinylamine homo- or -copolymer or a polyethyleneimine homopolymer, in particular a polyallylamine or polyethyleneimine homopolymer or a poly(vinylamine-co-acrylamid) copolymer.
The molecular weight of the anionic and cationic polymers used to prepare the bilayers may vary within wide limits depending on the desired characteristics such as adhesion on the bulk material, coating thickness and the like. In general, a weight average molecular weight of from about 5000 to about 5000000, preferably from 10000 to 1000000, more preferably 15000 to 500000, even more preferably from 20000 to 200000 and in particular from 40000 to 150000, has proven as valuable both for the anionic and cationic polymer forming the bilayer.
The anionic and cationic polymers used to prepare the bilayers are in general water-soluble. The anionic and cationic polymers forming the bilayers of the invention are known and the majority of them is commercially available, or they may be prepared according to methods known in the art. Polyallylamines comprising modifier units are known, for example, from EP-A-1002807.
The formation and application of the bilayers on the bulk material surface may be accomplished according to processes known per se. For example, the bulk material is immersed in a solution of the anionic and cationic polymer, or one or more layers each of the anionic and cationic polymer are successively deposited on the modified bulk material surface, for example, by dipping, spraying, printing, spreading, pouring, rolling, spin coating or vacuum vapor deposition, spraying or particularly dipping being preferred. Following the deposition of one ionic polymer the bulk material may be rinsed or dried before the deposition of the next ionic polymer having opposite charges. However, it is preferred to omit a rinsing or drying step between the attachment of the first and second ionic polymer.
A preferred dip method involves the steps of (i) applying a coating of a first ionic polymer, for example of a cationic or preferably of an anionic polymer, to the bulk material by immersing the bulk material in a solution of the first ionic polymer; (ii) optionally, rinsing the bulk material by immersing it in a rinsing solution; (iii) optionally, drying said bulk material; and (iv) applying a coating of a second ionic polymer having charges opposite of the charges of the first ionic polymer, for example an anionic or preferably a cationic polymer, to the bulk material by immersing the bulk material in a solution of the second ionic polymer. A more preferred dip method involves the steps of applying a coating of the first and second ionic polymer by immersing the bulk material successively in a solution each of the first and second ionic polymer without a rinsing or drying step in between. A further dip method involves immersing the bulk material in a solution comprising both the anionic and cationic polymer.
The dip solutions of the anionic and cationic polymer in general comprise the respective polymer diluted in one or more different solvents. Suitable solvents are, for example, water or an aqueous solution comprising a water-miscible organic solvent, for example a C1-C4-alkanol such as methanol or ethanol; the preferred solvent is pure water. The aqueous solutions of the cationic or anionic polymer advantageously each have a slightly acidic pH value, for example a pH from about 2 to about 5 and preferably from about 2.5 to about 4.5. The concentration of the dip solutions may vary within wide limits depending, for example, on the particular ionic polymer involved. However, it is generally preferred to formulate relatively dilute solutions of the ionic polymers. A preferred anionic or cationic polymer concentration is from about 0.0001 to about 0.25 weight percent, more preferably from 0.0005 to 0.15 weight percent and in particular from 0.001 to 0.1 percent by weight, relative to the total weight of the solution.
A suitable rinsing solution, if used, is preferably an aqueous solution, in particular an aqueous solution buffered at a pH of about 2 to about 7, more preferably from 2 to 5 and even more preferably from 2.5 to 4.5.
Partial drying or removal of excess rinsing solution from the surface between solution applications, if applicable, may be accomplished by a number of means known in the art. While the bulk material may be partially dried by merely allowing the lens to remain in an air atmosphere for a certain period of time, it is preferable to accelerate the drying by application of a mild stream of air to the surface. The flow rate may be adjusted as a function of the strength of the material being dried and the mechanical fixturing of the material. It should be noted that there is no requirement to completely dry the bulk material. The xe2x80x9cpartial dryingxe2x80x9d step, as used herein, refers to a removal of droplets of solution which cling to the lens surface, rather than a desiccation of the lens. Thus, it is preferred to dry only to the extent that any water or solution film on the surface is removed.
The thickness of the coating may be adjusted by addition of one or more salts, such as sodium chloride, to the ionic polymer solution. A preferred salt concentration is about 0.1 to about 2.0 weight percent. As the salt concentration is increased, the polyelectrolyte takes on a more globular conformation. However, if the concentration is raised too high, the polyelectrolyte will not deposit well, if at all, on the lens surface. A more preferred salt concentration is about 0.7 to about 1.3 weight percent.
The bilayer formation process may be repeated a plurality of times, for example from 1 to 24 times, preferably from 1 to 14 times, more preferably from 1 to 9 times; according to one embodiment just one bilayer is deposited.
The immersion time for each of the coating and optional rinsing steps may vary depending on a number of factors. In general a rinsing time of from about 30 seconds to about 30 minutes, prefereably from 1 to 20 minutes, more preferably 1 to 10 minutes and in particular 1 to 6 minutes has proven as valuable. The immersion in the polymer solutions takes place, for example, at room temperature or at elevated temperature, preferably at room temperature, for example at a temperature of from 15 to 30xc2x0 C. Following the dipping steps the bulk material may be subjected to a heat treatment in order to compact or stabilize the bilayer(s) on the bulk material surface.
Instead of coating the bulk material by means of a dip technique, said coating may also take place using spray coating techniques, wherein the above given conditions and features concerning solvents, concentrations, presence of salts, pH, temperature, number and sequence of coating steps, optional rinsing or drying steps apply accordingly. Spray coating technique in this context comprises any known process in the art including, for example, conventional techniques of applying a fluid, or techniques using ultrasonic energy, or electrostatic spray coating techniques. In addition a mixture of dip and spray techniques may also be employed.
In addition, if the polyionic material on the material surface consists of one single ionic polymer only, said ionic polymer may be applied to the surface as described above, in particular by dipping or spraying.
According to the above-mentioned methods bulk materials are obtained that comprise one polyelectrolyte or preferably one or more bilayers of polyelectrolytes adsorbed and/or heteropolarly bound on the surface. Due to this modification the surface is provided with functional groups, for example with carboxy, sulfone, sulfato, phosphono or phosphato groups or with primary, secondary or tertiary amine groups; said functional groups, preferably the carboxy groups or in particular the primary or secondary amino groups, may be further reacted with a functional initiator for radical polymerization.
Polymerization initiators bound to the polyionic material that is attached to the bulk material surface are typically those that are initiating a radical polymerization of ethylenically unsaturated compounds. The radical polymerization may be induced thermally, or preferably by irradiation.
Suitable thermal polymerization initiators are known to the skilled artisan and comprise for example peroxides, hydroperoxides, azo-bis(alkyl- or cycloalkylnitriles), persulfates, percarbonates or mixtures thereof. An example for a functionalized thermal initiator is 4,4xe2x80x2-azo-bis(4-cyanovaleric acid) or derivatives thereof.
Initiators for the radiation-induced polymerization are particularly functional photoinitiators having a photoinitiator part and in addition a functional group that is coreactive with functional groups of the bilayers, particularly with amino or carboxy groups. The photoinitiator part may belong to different types, for example to the thioxanthone type and preferably to the benzoin type. Suitable functional groups that are coreactive with the bilayers attached to the surface of the bulk material are for example a carboxy, hydroxy, epoxy or particularly an isocyanato group.
Preferred polymerization initiators for use in the present invention are the photoinitiators of formulae (I) and (Ia) as disclosed in U.S. Pat. No. 5,527,925, those of the formula (I) as disclosed in PCT application WO 96/20919, or those of formulae II and III including formulae IIa-IIy and IIIg as disclosed in EP-A-0281941, particularly formulae IIb, IIi, IIm, IIn, IIp, IIr, IIs, IIx and IIIg therein. The respective portion of said three documents including the definitions and preferences given for the variables in said formulae are herewith included by reference.
The polymerization initiator moieties are preferably derived from a functional photoinitiator of the formula 
wherein Z is bivalent xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94 or xe2x80x94NR22xe2x80x94; Z1 is xe2x80x94Oxe2x80x94, xe2x80x94Oxe2x80x94(O)C-, xe2x80x94C(O)xe2x80x94Oxe2x80x94 or xe2x80x94Oxe2x80x94C(O)xe2x80x94Oxe2x80x94; R13 is H, C1-C12-alkyl, C1-C12-alkoxy or N-C1-C12-alkylamino; R14 and R15 are each independently of the other H, linear or branched C1-C8-alkyl, C1-C8-hydroxyalkyl or C6-C10-aryl, or the groups R14xe2x80x94(O)b1xe2x80x94 and R14xe2x80x94(O)b2xe2x80x94 together are xe2x80x94(CH2)cxe2x80x94 wherein c is an integer from 3 to 5, or the groups R14xe2x80x94(O)b1xe2x80x94, R14xe2x80x94(O)b2xe2x80x94 and R15xe2x80x94(O)b3xe2x80x94 together are a radical of the formula 
R12 is a direct bond or linear or branched C1-C8-alkylene that is unsubstituted or substituted by xe2x80x94OH and/or is uninterrupted or interrupted by one or more groups xe2x80x94Oxe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94 or xe2x80x94Oxe2x80x94C(O)xe2x80x94Oxe2x80x94; R11xe2x80x2 is branched C3-C18-alkylene, unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C6-C10-arylene, or unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C7-C18-aralkylene unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C3-C8-cycloalkylene, unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C3-C8-cycloalkylene-CyH2yxe2x80x94 or unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted xe2x80x94CyH2yxe2x80x94(C3-C8-cycloalkylenee)-CyH2yxe2x80x94 wherein y is an integer from 1 to 6; R16 independently has the same definitions as R11xe2x80x2 or is linear C3-C18-alkylene; R22 is linear or branched C1-C6-alkyl; T is bivalent xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Sxe2x80x94, C1-C8-alkylene 
Z2 is a direct bond or xe2x80x94Oxe2x80x94(CH2)dxe2x80x94 wherein d is an integer from 1 to 6 and the terminal CH2 group of which is linked to the adjacent T in formula (10c); R17 is H, C1-C12-alkyl, C1-C12-alkoxy, N-C1-C12-alkylamino or xe2x80x94NR2,R26 wherein R25 is C1-C8-alkyl and R26 is H or C1-C8-alkyl; R18 is linear or branched C1-C8-alkyl, C2-C8-alkenyl or C6-C10-aryl-C1-C8-alkyl; R19 independently of R18 has the same definitions as R18 or is C6-C10-aryl, or R18 and R19 together are xe2x80x94(CH2)exe2x80x94 wherein e is an integer from 2 to 6; R20 and R21 are each independently of the other linear or branched C1-C8-alkyl that may be substituted by C1-C4-alkoxy, or C6-C10-aryl-C1-C8-alkyl or C2-C8-alkenyl; or R20 and R21 together are xe2x80x94(CH2)11xe2x80x94Z3xe2x80x94(CH2)f2xe2x80x94 wherein Z3 is a direct bond, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94 or xe2x80x94NR26-, and R26 is H or C1-C8-alkyl and f1 and f2 are each independently of the other an integer from 2 to 4; R23 and R24 are each independently of the other H, C1-C8-alkyl, C3-C8-cycloalkyl, benzyl or phenyl; and a, a1, b1, b2 and b3 are each independently of the other 0 or 1; subject to the provisos that b1 and b2 are each 0 when R15 is H; that the total of (b1+b2+b3) is not exceeding 2; and that a is 0 when R12 is a direct bond.
A preferred sub-group of compounds of formula (10a) or (10b) comprises those wherein, b1 and b2 are each 0; Z and Z1 are each bivalent xe2x80x94Oxe2x80x94; b3 is 0 or 1; R14 is C1-C4-alkyl or phenyl, or both groups R14 together are tetramethylene or pentamethylene; R15 is C1-C4-alkyl or H, R13 is hydrogen; a and a1 are each independently 0 or 1; R12 is linear or branched C2-C4-alkylene, or is a direct bond, in which case a is 0; R11xe2x80x2 is branched C5-C10-alkylene, phenylene or phenylene substituted by from 1 to 3 methyl groups, benzylene or benzylene substituted by from 1 to 3 methyl groups, cyclohexylene or cyclohexylene substituted by from 1 to 3 methyl groups, cyclohexyl-CyH2yxe2x80x94 or xe2x80x94CyH2y-cyclohexyl-CyH2yxe2x80x94 or cyclohexyl-CyH2yxe2x80x94 or xe2x80x94CyH2y-cyclohexyl-CyH2yxe2x80x94 substituted by from 1 to 3 methyl groups; y is 1 or 2; and R16 has the same definitions as R11, or is linear C3-C10alkylene.
An especially preferred sub-group of compounds of formula (10a) or (10b) comprises those wherein, b1 and b2 are each 0, Z and Z. are each bivalent xe2x80x94Oxe2x80x94, b3 is 0 or 1; R14 is methyl or phenyl, or both groups R14 together are pentamethylene; R15 is methyl or H; R13 is hydrogen; a is 1 and R12 is ethylene, or a is 0 and R12 is a direct bond; a1 is 0 or 1; R11xe2x80x2 is branched C1-C10-alkylene, phenylene or phenylene substituted by from 1 to 3 methyl groups, benzylene or benzylene substituted by from 1 to 3 methyl groups, cyclohexylene or cyclohexylene substituted by from 1 to 3 methyl groups, cyclohexyl-CH2xe2x80x94 or cyclohexyl-CH2-substituted by from 1 to 3 methyl groups; R16 has the same definitions as R11 or is linear C5-C10alkylene.
A preferred sub-group of compounds of formula (10c) comprises those wherein T is bivalent xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Sxe2x80x94 or xe2x80x94(CH2)yxe2x80x94 wherein y is an integer from 1 to 6; Z2 is a direct bond or xe2x80x94Oxe2x80x94(CH2)yxe2x80x94 wherein y is an integer from 1 to 6 and the terminal CH2 group of which is linked to the adjacent T in formula (10c); R17 is H, C1-C12-alkyl or C1-C12-alkoxy; R18 is linear C1-C8-alkyl, C2-C8-alkenyl or C6-C10-aryl-C1-C8-alkyl; R19 independently of R18 has the same definitions as R18 or is C6-C10-aryl, or R15 and R19 together are xe2x80x94(CH2)exe2x80x94 wherein e is an integer from 2 to 6; R20 and R21 are each independently of the other linear or branched C1-C8-alkyl that may be substituted by C1-C4-alkoxy, or C6-C10-aryl-C1-C8-alkyl or C2-C8-alkenyl; or R20 and R21 together are xe2x80x94(CH2)f1xe2x80x94Z3xe2x80x94(CH2)f2xe2x80x94 wherein Z3 is a direct bond, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94 or xe2x80x94NR26xe2x80x94, and R26 is H or C1-C8-alkyl and f1 and f2 are each independently of the other an integer from 2 to 4; and R16 is branched C6-C10-alkylene, phenylene or phenylene substituted by from 1 to 3 methyl groups, benzylene or benzylene substituted by from 1 to 3 methyl groups, cyclohexylene or cyclohexylene substituted by from 1 to 3 methyl groups, cyclohexylene-CH2- or cyclohexylene-CH2xe2x80x94 substituted by from 1 to 3 methyl groups.
An especially preferred sub-group of compounds of formula (10c) comprises those wherein T is bivalent xe2x80x94Oxe2x80x94; Z2 is xe2x80x94Oxe2x80x94(CH2)yxe2x80x94 wherein y is an integer from 1 to 4 and the terminal CH2 group of which is linked to the adjacent T in formula (10c); R17 is H; R18 is methyl, allyl, tolylmethyl or benzyl, R19 is methyl, ethyl, benzyl or phenyl, or R18 and R19 together are pentamethylene, R20 and R2, are each independently of the other C1-C4-alkyl or R20 and R21 together are xe2x80x94CH2CH2OCH2CH2xe2x80x94, and R16 is branched C6-C10-alkylene, phenylene or phenylene substituted by from 1 to 3 methyl groups, benzylene or benzylene substituted by from 1 to 3 methyl groups, cyclohexylene or cyclohexylene substituted by from 1 to 3 methyl groups, cyclohexylene-CH2- or cyclohexylene-CH2-substituted by from 1 to 3 methyl groups.
Some examples of especially preferred functional photoinitiators are the compounds of formulae 
wherein R27 is a radical 
In a preferred embodiment of the invention, the covalent bonding between the bilayer(s) that is/are attached to the bulk material surface and the photoinitiator occurs via reaction of an amino or carboxy group, particularly an amino group, of the modified bulk material surface with an isocyanato group of the photoinitiator, for example using a photoinitiator of the above formula (10b), (10c), (11a), (11b) or (11c). Suitable methods for this are known, for example, from the above-mentioned documents. The reaction may be carried out, for example, at elevated temperature, for example from 0xc2x0 to 100xc2x0 C. and preferably at room temperature, and optionally in the presence of a catalyst. After the reaction, excess compounds can be removed, for example, with solvents.
According to a preferred embodiment of the invention the bulk material comprises on its modified surface xe2x80x94NH2 and/or xe2x80x94NHxe2x80x94 groups, that are coreactive with isocyanato groups, some of whose H atoms have been substituted by radicals of the formulae 
wherein for the variables R11xe2x80x2-R21, T, Z, Z1, Z2, a, b1, b2 and b3 the above-given meanings and preferences apply.
In another embodiment of the invention, the covalent bonding between the modified bulk material surface and the photoinitiator occurs via reaction of a carboxy or isocyanato group of the bilayer attached to the bulk material with a hydroxy, amino or alkylamino group of the photoinitiator, for example using a photoinitiator of the above formula (10a). Isocyanato groups may be attached to the bilayer, for example, by first reacting an above-mentioned modified bulk material containing a bilayer with amino groups on the surface, selectively with one isocyanato group of a diisocyanate of formula OCNxe2x80x94R11xe2x80x2xe2x80x94NCO, wherein R11xe2x80x2 has the above-given meanings; the thus modified bulk material then may be reacted with a photoinitiator of the above-mentioned formula (10a). The reaction of carboxy groups of the bilayer with hydroxy or amino groups of the photoinitiator of formula (10a) is well-known in the art and may be carried out, for example, as described in textbooks of organic chemistry.
A hydrophilic monomer useful to provide the hydrophilic surface coating (b) on the initiator-modified bulk material surface is typical a monomer that yields as homopolymer a polymer that is water-soluble or can absorb at least 10% by weight of water. Examples of preferred hydrophilic monomers are hydroxy-substituted C2-C4-alkyl acrylates and methacrylates, acrylamide, W methacrylamide, N,N-di-C1-C4-alkyl acrylamides and methacrylamides, ethoxylated acrylates and methacrylates, hydroxy-substituted C2-C4-alkyl acrylamides and methacrylamides, hydroxy-substituted C1-C4-alkyl vinyl ethers, sodium ethylenesulfonate, sodium styrenesulfonate, 2-acrylamido-2-methylpropanesulfonic acid, N-vinylpyrrole, N-vinylsuccinimide, N-vinylpyrrolidone, 2- or 4-vinylpyridine, acrylic acid, methacrylic acid, amino-(the term xe2x80x9caminoxe2x80x9d also including quaternary ammonium), mono-C1-C4-alkylamino- or di-C1-C4-alkylamino-C1-C4-alkyl acrylates and methacrylates, allylalcohol and the like. Hydroxy-substituted or N,N-di-C1-C2-alkylamino-substituted C2-C4alkyl(meth)acrylates, five- to seven-membered N-vinyl lactams, N,N-di-C1-C4alkyl(meth)acrylamides and vinylically unsaturated carboxylic acids having a total of from 3 to 5 carbon atoms, for example, are preferred.
Examples of preferred hydrophilic vinylic monomers include hydroxyethyl methacrylate, hydroxy-ethyl acrylate, acrylamide, methacrylamide, N,N-dimethylacrylamide, allyl alcohol, N-vinylpyrrolidone, acrylic acid, methacrylic acid and N,N-dimethylaminoethyl methacrylate.
Preferably the hydrophilic surface coating (b) on the bulk material (a) is obtained using a suitable macromonomer. A preferred macromonomer is, for example, of formula 
wherein R1 is hydrogen, C1-C6-alkyl or a radical xe2x80x94COORxe2x80x2;
R, Rxe2x80x2 and R1xe2x80x2 are each independently of the other hydrogen or C1-C6-alkyl;
A is a direct bond or is a radical of formula
xe2x80x94C(O)xe2x80x94(A1)nxe2x80x94Xxe2x80x94xe2x80x83xe2x80x83(2a) 
or
xe2x80x94(A2)mxe2x80x94NHxe2x80x94C(O)xe2x80x94Xxe2x80x94xe2x80x83xe2x80x83(2b); 
or
xe2x80x94(A2)mxe2x80x94Xxe2x80x94C(O)xe2x80x94xe2x80x83xe2x80x83(2c); 
or
xe2x80x94C(O)xe2x80x94NHxe2x80x94C(O)xe2x80x94Xxe2x80x94xe2x80x83xe2x80x83(2d); 
or
xe2x80x94C(O)xe2x80x94X1xe2x80x94(alk*)xe2x80x94Xxe2x80x94C(O)xe2x80x94xe2x80x83xe2x80x83(2e); 
or A and R1, together with the adjacent double bond, are a radical of formula 
A1 is xe2x80x94O-C2-C12-alkylene which is unsubstituted or substituted by hydroxy, or is xe2x80x94O-C2-C12-alkylene-NHxe2x80x94C(O)xe2x80x94 or xe2x80x94O-C2-C12-alkylene xe2x80x94Oxe2x80x94C(O)xe2x80x94NHxe2x80x94R11xe2x80x94NHxe2x80x94C(O)xe2x80x94, wherein R11 is linear or branched C1-C18-alkylene or unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C6-C10-arylene, C7-C18-aralkylene, C6-C10-arylene-C1-C2-alkylene-C6-C10-arylene, C3-C8-cycloalkylene, C3-C8-cycloalkylene-C1-C6-alkylene, C3-C8-cycloalkylene-C1-C2-alkylene-C3-C8-cycloalkylene or C1-C6-alkylene-C3-C8-cycloalkylene-C1-C6-alkylene;
A2 is C1-C8-alkylene; phenylene or benzylene;
m and n are each independently of the other the number 0 or 1;
X, X1 and Xxe2x80x2 are each independently of the other a bivalent group xe2x80x94Oxe2x80x94 or xe2x80x94NRxe2x80x3, wherein Rxe2x80x3 is hydrogen or C1-C6-alkyl;
(alk*) is C2-C12-alkylene;
and (oligomer) denotes
(i) the radical of a telomer of formula 
wherein (alk) is C2-C12-alkylene,
Q is a monovalent group that is suitable to act as a polymerization chain-reaction terminator,
p and q are each independently of another an integer from 0 to 250, wherein the total of (p+q) is an integer from 2 to 250,
and B and Bxe2x80x2 are each independently of the other a 1,2-ethylene radical derivable from a copolymerizable vinyl monomer by replacing the vinylic double bond by a single bond, at least one of the radicals B and Bxe2x80x2 being substituted by a hydrophilic substituent; or
(ii) the radical of an oligomer of the formula 
wherein R28 is hydrogen or unsubstituted or hydroxy-substituted C1-C12-alkyl, u is an integer from 2 to 250 and Qxe2x80x2 is a radical of a polymerization initiator; or
(iii) the radical of formula 
wherein R28, X and u are as defined above, or
(iv) the radical of an oligomer of formula 
wherein R2 and R2xe2x80x2 are each independently C1-C4-alkyl, Anxe2x88x92 is an anion, v is an integer from 2 to 250, and Qxe2x80x3 is a monovalent group that is suitable to act as a polymerization chain-reaction terminator; or
(v) the radical of an oligopeptide of formula
xe2x80x94(CHR4xe2x80x94C(O)xe2x80x94NH)txe2x80x94CHR4xe2x80x94COOHxe2x80x83xe2x80x83(3d) 
or
xe2x80x94CHR4xe2x80x94(NHxe2x80x94C(O)xe2x80x94CHR4)txe2x80x94NH2xe2x80x83xe2x80x83(3dxe2x80x2), 
wherein R4 is hydrogen or C1-C4-alkyl which is unsubstituted or substituted by hydroxy, carboxy, carbamoyl, amino, phenyl, o-, m- or p-hydroxyphenyl, imidazolyl, indolyl or a radical xe2x80x94NHxe2x80x94C(xe2x95x90NH)xe2x80x94NH2 and t is an integer from 2 to 250, or the radical of an oligopeptide based on proline or hydroxyproline; or
(vi) the radical of a polyalkylene oxide of formula
xe2x80x94(alk**xe2x80x94O)zxe2x80x94[CH2xe2x80x94CH2xe2x80x94O]rxe2x80x94[CH2xe2x80x94CH(CH3)xe2x80x94O]sxe2x80x94R30xe2x80x83xe2x80x83(3e), 
wherein R30 is hydrogen or C1-C24-alkyl, (alk**) is C2-C4-alkylene, z is 0 or 1, r and s are each independently an integer from 0 to 250 and the total of (r+s) is from 2 to 250; or
(vii) the radical of an oligosaccharide;
subject to the provisos that
A is not a direct bond if (oligomer) is a radical of formula (3a);
A is a direct bond if (oligomer) is a radical of formula (3bxe2x80x2);
A is not a radical of formula (2c) or (2e) if (oligomer) is a radical of formula (3b), (3c), (3d), (3e) or is the radical of an oligosaccharide; and
A is a radical of formula (2c) or (2e) if (oligomer) is a radical of formula (3dxe2x80x2).
The following preferences apply to the variables contained in the definition of the macromonomer of formula (1):
Rxe2x80x2 is preferably hydrogen or C1-C4-alkyl, more preferably hydrogen or C1-C2-alkyl and particularly preferably hydrogen.
R1 is preferably hydrogen, methyl or carboxyl, and particularly preferably hydrogen.
R is preferably hydrogen or methyl.
X is preferably a bivalent group xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94. X is particularly preferably the group xe2x80x94NHxe2x80x94 if (oligomer) is a radical of formula (3a); (3c) or (3d), and is particularly preferably the group xe2x80x94Oxe2x80x94 if (oligomer) is a radical of formula (3b). Xxe2x80x2 is preferably xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94 and more preferably xe2x80x94NHxe2x80x94. X1 is preferably xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94.
R11 as alkylene is preferably a linear or branched C3-C14alkylene radical, more preferably a linear or branched C4-C12alkylene radical and most preferably a linear or branched C1-C10alkylene radical.
When R11 is arylene, it is, for example, naphthylene or especially phenylene, each of which may be substituted, for example, by C1-C4-alkyl or by C1-C4-alkoxy. Preferably, R., as arylene is 1,3- or 1,4-phenylene that is unsubstituted or substituted by C1-C4-alkyl or by C1-C4-alkoxy in the ortho-position to at least one linkage site. Examples of substituted arylene are 1-methyl-2,4-phenylene, 1,5-dimethyl-2,4-phenylene, 1-methoxy-2,4-phenylene and 1-methyl-2,7-naphthylene.
R11 as aralkylene is preferably naphthylalkylene and most preferably phenylalkylene. The alkylene group in aralkylene contains preferably from 1 to 12, more preferably from 1 to 6 and most preferably from 1 to 4 carbon atoms. Most preferably, the alkylene group in aralkylene is methylene or ethylene.
When R11 is cycloalkylene, it is preferably C5-C6cycloalkylene and most preferably cyclohexylene that is unsubstituted or substituted by methyl.
When R11 is cycloalkylene-alkylene, it is preferably cyclopentylene-C1-C4-alkylene and especially cyclohexylene-C1-C4-alkylene, each unsubstituted or mono- or poly-substituted by C1-C4-alkyl, especially methyl. More preferably, the group cycloalkylene-alkylene is cyclohexylene-ethylene and, most preferably, cyclohexylene-methylene, each unsubstituted or substituted in the cyclohexylene radical by from 1 to 3 methyl groups.
When R11 is alkylene-cycloalkylene-alkylene, it is preferably C1-C4-alkylene-cyclopentylene-C1-C4-alkylene and especially C1-C4-alkylene-cyclohexylene-C1-C4-alkylene, each unsubstituted or mono- or poly-substituted by C1-C4-alkyl, especially methyl. More preferably, the group alkylene-cycloalkylene-alkylene is ethylene-cyclohexylene-ethylene and, most preferably, is methylene-cyclohexylene-methylene, each unsubstituted or substituted in the cyclohexylene radical by from 1 to 3 methyl groups.
R11 as C3-C8-cycloalkylene-C1-C2-alkylene-C3-C8-cycloalkylene or C6-C10-arylene-C1-C2-alkylene-C6-C10-arylene is preferably C5-C6-cycloalkylene-methylene-C5-C6-cycloalkylene or phenylene-methylene-phenylene, each of which may be unsubstituted or substituted in the cycloalkyl or phenyl ring by one or more methyl groups.
The radical R11 has a symmetrical or, preferably, an asymmetrical structure. A preferred group of radicals R11 comprises those, wherein R11 is linear or branched C6-C10alkylene; cyclohexylene-methylene or cyclohexylene-methylene-cyclohexylene each unsubstituted or substituted in the cyclohexyl moiety by from 1 to 3 methyl groups; or phenylene or phenylene-methylene-phenylene each unsubstituted or substituted in the phenyl moiety by methyl. The bivalent radical R11 is derived preferably from a diisocyanate and most preferably from a diisocyanate selected from the group isophorone diisocyanate (IPDI), toluylene-2,4-diisocyanate (TDI), 4,4xe2x80x2-methylenebis(cyclohexyl isocyanate), 1,6-diisocyanato-2,2,4-trimethyl-n-hexane (TMDI), methylenebis(phenyl isocyanate), methylenebis(cyclohexyl-4-isocyanate) and hexamethylene diisocyanate (HMDI).
Preferred meanings of A1 are unsubstituted or hydroxy-substituted xe2x80x94Oxe2x80x94C2-C8-alkylene or a radical xe2x80x94Oxe2x80x94C2-C6-alkylenexe2x80x94NHxe2x80x94C(O)xe2x80x94 and particularly xe2x80x94Oxe2x80x94(CH2)2-4xe2x80x94, xe2x80x94Oxe2x80x94CH2xe2x80x94CH(OH)xe2x80x94CH2xe2x80x94 or a radical xe2x80x94Oxe2x80x94 (CH2)2-4xe2x80x94NHxe2x80x94C(O)xe2x80x94. A particularly preferred meaning of A1 is the radical xe2x80x94Oxe2x80x94(CH2)2xe2x80x94NHxe2x80x94C(O)xe2x80x94.
A2 is preferably C1-C6-alkylene, phenylene or benzylene, more preferably C1-C4-alkylene and even more preferably C1-C2-alkylene.
n is an integer of 0 or preferably 1. m is preferably an integer of 1.
R1xe2x80x2 is preferably hydrogen or methyl and particularly preferably hydrogen.
In case that (oligomer) is a radical of formula (3a), (3b), (3c), (3d), (3e) or is the radical of an oligosaccharide. A preferably denotes a radical of formula (2a) or (2b) and particularly preferably a radical of formula (2a), wherein the above given meanings and preferences apply for the variables contained therein.
A preferred group of hydrophilic macromonomers according to the invention comprises compounds of the above formula (1), wherein R is hydrogen or methyl, R1 is hydrogen, methyl or carboxyl, R1xe2x80x2 is hydrogen, A is a radical of the formula (2a) or (2b) and (oligomer) is a radical of formula (3a), (3b), (3c), (3d), (3e) or is the radical of an oligosaccharide. An even more preferred group of hydrophilic macromonomers comprises compounds of the above formula (1), wherein R is hydrogen or methyl, R1 and R1xe2x80x2 are each hydrogen, A is a radical of the formula (2a) and (oligomer) is a radical of formula (3a). A further group of preferred macromonomers comprises compounds of formula (1), wherein A is a radical of formula (2e) above and (oligomer) is a radical of formula (3a).
(alk) and (alk*) are each independently preferably C2-C8-alkylene, more preferably C2-C6-alkylene, even more preferably C2-C4-alkylene and particularly preferably 1,2-ethylene. The alkylene radicals (alk) and (alk*) may be branched or preferably linear alkylene radicals.
Q is for example hydrogen.
The total of (p+q) is preferably an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 10 to 50. In a preferred embodiment of the invention q is 0 and p is an integer from 2 to 250, preferably from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 10 to 50. In a further preferred embodiment p is from 4 to 99, q is from 1 to 96 and the total 30 of (p+q) is from 5 to 100.
Suitable hydrophilic substituents of the radicals B or Bxe2x80x2 may be non-ionic, anionic, cationic or zwitterionic substituents. Accordingly, the telomer chain of formula (3a) that contains monomer units B and/or Bxe2x80x2 may be a charged chain containing anionic, cationic and/or zwitterionic groups or may be an uncharged chain. In addition, the telomer chain may comprise a copolymeric mixture of uncharged and charged units. The distribution of the charges within the telomer, if present, may be random or blockwise.
In one preferrred embodiment of the invention, the telomer radical of formula (3a) is composed solely of non-ionic monomer units B and/or Bxe2x80x2. In another preferred embodiment of the invention, the telomer radical of formula (3a) is composed solely of ionic monomer units B and/or Bxe2x80x2, for example solely of cationic monomer units or solely of anionic monomer units. Still another preferred embodiment of the invention is directed to telomer radicals of formula (3a) comprising nonionic units B and ionic units Bxe2x80x2.
Suitable non-ionic substituents of B or Bxe2x80x2 include for example a radical C1-C6-alkyl which is substituted by one or more same or different substituents selected from the group consisting of xe2x80x94OH, C1-C4-alkoxy and xe2x80x94NR9R9xe2x80x2, wherein R9 and R1xe2x80x2 are each independently of another hydrogen or unsubstituted or hydroxy-substituted C1-C6-alkyl or phenyl; phenyl which is substituted by hydroxy, C1-C4-alkoxy or xe2x80x94NR9R9xe2x80x2, wherein R1 and R1xe2x80x2 are as defined above; a radical xe2x80x94COOY, wherein Y is C1-C24-alkyl which is unsubstituted or substituted, for example, by hydroxy, C1-C4-alkoxy, xe2x80x94Oxe2x80x94Si(CH3)3, xe2x80x94NR9R9xe2x80x2 wherein R1 and R1xe2x80x2 are as defined above, a radical xe2x80x94Oxe2x80x94(CH2CH20)1-24-E wherein E is hydrogen or C1-C6-alkyl, or a radical xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G, wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide with 1 to 8 sugar units or is a radical xe2x80x94Oxe2x80x94(CH2CH20)1-24xe2x80x94E, wherein E is as defined above, or Y is C5-C8-cycloalkyl which is unsubstituted or substituted by C1-C4-alkyl or C1-C4-alkoxy, or is unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted phenyl or C7-C12-aralkyl; xe2x80x94CONY1Y2 wherein Y1 and Y2 are each independently hydrogen, C1-C12-alkyl, which is unsubstituted or substituted for example by hydroxy, C1-C4-alkoxy or a radical xe2x80x94Oxe2x80x94(CH2CH20)124-E wherein E is as defined above, or Y1 and Y2 together with the adjacent N-atom form a five- or six-membered heterocyclic ring having no additional heteroatom or one additional oxygen or nitrogen atom; a radical xe2x80x94OY3, wherein Y3 is hydrogen; or C1-C12-alkyl which is unsubstituted or substituted by xe2x80x94NR9R9xe2x80x2; or is a radical xe2x80x94C(O)xe2x80x94C1-C4-alkyl; and wherein R1 and R9xe2x80x2 are as defined above; or a five- to seven-membered heterocyclic radical having at least one N-atom and being bound in each case via said nitrogen atom.
Suitable anionic substituents of B or Bxe2x80x2 include for example C1-C6-alkyl which is substituted by xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2 and xe2x80x94COOH; phenyl which is substituted by one or more same or different substituents selected from the group consisting of xe2x80x94SO3H, xe2x80x94COOH, xe2x80x94OH and xe2x80x94CH2xe2x80x94SO3H; xe2x80x94COOH; a radical xe2x80x94COOY4, wherein Y4 is C1-C24-alkyl which is substituted for example by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2 or by a radical xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94Gxe2x80x2 wherein Gxe2x80x2 is the radical of an anionic carbohydrate; a radical xe2x80x94CONY5Y6 wherein Y5 is C1-C24-alkyl which is substituted by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, or xe2x80x94OPO3H2 and Y6 independently has the meaning of Y5 or is hydrogen or C1-C12-alkyl; or xe2x80x94SO3H; or a salt thereof, for example a sodium, potassium, ammonium or the like salt thereof.
Suitable cationic substituents of B or Bxe2x80x2 include C1-C12-alkyl which is substituted by a radical xe2x80x94NR9R9xe2x80x2R9xe2x80x3+Anxe2x88x92, wherein R9R9xe2x80x2 and R9xe2x80x3 are each independently of another hydrogen or unsubstituted or hydroxy-substituted C1-C6-alkyl or phenyl, and An is an anion; or a radical xe2x80x94C(O)OY7, wherein Y7 is C1-C24-alkyl which is substituted by xe2x80x94NR9R9xe2x80x2R9xe2x80x3+Anxe2x88x92 and is further unsubstituted or substituted for example by hydroxy, wherein R11 R9xe2x80x2, R9xe2x80x3 and Anxe2x88x92 are as defined above.
Suitable zwitterionic substituents of B or Bxe2x80x2 include a radical xe2x80x94R3xe2x80x94Zw, wherein R3 is a direct bond or a functional group, for example a carbonyl, carbonate, amide, ester, dicarboanhydride, dicarboimide, urea or urethane group; and Zw is an aliphatic moiety comprising one anionic and one cationic group each.
The following preferences apply to the hydrophilic substituents of B and Bxe2x80x2:
(i) non-ionic substituents:
Preferred alkyl substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is substituted by one or more substituents selected from the group consisting of xe2x80x94OH and xe2x80x94NR9R9xe2x80x2, wherein R9 and R9xe2x80x2 are each independently of another hydrogen or C1-C4-alkyl, preferably hydrogen, methyl or ethyl and particularly preferably hydrogen or methyl, for example xe2x80x94CH2xe2x80x94NH2, xe2x80x94CH2xe2x80x94N(CH3)2.
Preferred phenyl substituents of B or Bxe2x80x2 are phenyl which is substituted by xe2x80x94NH2 or N(C1-C2-alkyl)2, for example o-, m- or p-aminophenyl.
In case that the hydrophilic substituent of B or Bxe2x80x2 is a radical xe2x80x94COOY, Y as optionally substituted alkyl is preferably C1-C12-alkyl, more preferably C1-C6-alkyl, even more preferably C1-C4-alkyl and particularly preferably C1-C2-alkyl, each of which being unsubstituted or substituted as mentioned above. In case that the alkyl radical Y is substituted by xe2x80x94NR9R9xe2x80x2, the above-given meanings and preferences apply for R9 and R9xe2x80x2. Examples of suitable saccharide substituents xe2x80x94Oxe2x80x94G of the alkyl radical Y that is substituted by xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G are the radical of a mono- or disaccharide, for example glucose, acetyl glucose, methyl glucose, glucosamine, N-acetyl glucosamine, glucono lactone, mannose, galactose, galactosamine, N-acetyl galactosamine, fructose, maltose, lactose, fucose, saccharose or trehalose, the radical of an anhydrosaccharide such as levoglucosan, the radical of a glucosid such as octylglucosid, the radical of a sugar alcohol such as sorbitol, the radical of a sugar acid derivative such as lactobionic acid amide, or the radical of an oligosaccharide with a maximum of 8 sugar units, for example fragments of a cyclodextrin, starch, chitosan, maltotriose or maltohexaose. The radical xe2x80x94Oxe2x80x94G preferably denotes the radical of a mono- or disaccharide or the radical of a cyclodextrin fragment with a maximum of 8 sugar units. Particular preferred saccharide radicals xe2x80x94Oxe2x80x94G are the radical of trehalose or the radical of a cyclodextrin fragment. In case that the alkyl radical Y is substituted by a radical xe2x80x94Oxe2x80x94(CH2CH20)1-24 xe2x80x94E or xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is xe2x80x94Oxe2x80x94(CH2CH20),24-E, the number of (CH2CH2O) units is preferably from 1 to 12 in each case and more preferably from 2 to 8. E is preferably hydrogen or C1-C2-alkyl.
Y as C5-C8-cycloalkyl is for example cyclopentyl or preferably cyclohexyl, each of which being unsubstituted or substituted for example by 1 to 3 C1-C2-alkyl groups. Y as C7-C12-aralkyl is for example benzyl.
Preferred nonionic radicals xe2x80x94COOY are those wherein Y is C1-C4-alkyl; or C2-C4-alkyl which is substituted by one or two substituents selected from the group consisting of hydroxy; C1-C2-alkoxy; xe2x80x94Oxe2x80x94Si(CH3)3; and xe2x80x94NR9R9xe2x80x2 wherein R9 and R1xe2x80x2 are each independently of another hydrogen or C1-C4-alkyl; or Y is a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH20)1,12-E wherein E is hydrogen or C1-C2-alkyl; or is a radical -C2-C4-alkylenexe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G, wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide.
More preferred non-ionic radicals xe2x80x94COOY are those wherein Y is C1-C2-alkyl, particularly methyl; or C2-C4-alkyl which is substituted by one or two substituents selected from the group consisting of xe2x80x94OH and xe2x80x94NR9R9xe2x80x2 wherein R9 and R9xe2x80x2 are each independently of another hydrogen or C1-C2-alkyl; or a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH20)112xe2x80x94E wherein E is hydrogen or C1-C2-alkyl; or is a radical xe2x80x94C2-C4-alkylenexe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide.
Particularly preferred radicals xe2x80x94COOY comprise those wherein Y is C2-C3-alkyl, which is substituted by hydroxy or N,N-di-C1-C2-alkylamino, or is a radical -C2-C3-alkylenexe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose.
Preferred non-ionic substituents xe2x80x94C(O)xe2x80x94NY1Y2 of B or Bxe2x80x2 are those wherein Y1 and Y2 are each independently of the other hydrogen or C1-C4-alkyl which is unsubstituted or substituted by hydroxy; or Y1 and Y2 together with the adjacent N-atom form a heterocyclic 6-membered ring having no further heteroatom or having one further N- or O-atom. Even more preferred meanings of Y1 and Y2, independently of each other, are hydrogen or C1-C2-alkyl which is unsubstituted or substituted by hydroxy; or Y1 and Y2 together with the adjacent N-atom form a N-C1-C2-alkyl-piperazino or morpholino ring. Particularly preferred non-ionic radicals xe2x80x94C(O)xe2x80x94NY1Y2 are those wherein Y1 and Y2 are each independently of the other hydrogen or C1-C2-alkyl; or Y1 and Y2 together with the adjacent N-atom form a morpholino ring.
Preferred non-ionic substituents xe2x80x94OY3 of B or Bxe2x80x2 are those wherein Y3 is hydrogen, C1-C4-alkyl which is unsubstituted or substituted by xe2x80x94NH2 or xe2x80x94N(C1-C2-alkyl)2, or is a group xe2x80x94C(O)C1-C2-alkyl. Y3 is particularly preferred hydrogen or acetyl.
Preferred non-ionic heterocyclic substituents of B or Bxe2x80x2 are a 5- or 6-membered heteroaromatic or heteroaliphatic radical having one N-atom and in addition no further heteroatom or an additional N- or O-heteroatom, or is a 5 to 7-membered lactame. Examples of such heterocyclic radicals are N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methyl pyridin-5-yl, 2-, 3-oder 4-hydroxypyridinyl, N-xcex5-caprolactamyl, N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl or 4xe2x80x94N-methylpiperazin-1-yl, particularly N-morpholinyl or N-pyrrolidonyl.
A group of preferred non-ionic substituents of B or Bxe2x80x2 comprises C1-C2-alkyl, which is unsubstituted or substituted by xe2x80x94OH or xe2x80x94NR9R9xe2x80x2, wherein R9 and R9xe2x80x2 are each independently of the other hydrogen or C1-C2-alkyl; a radical xe2x80x94COOY wherein Y is C1-C4-alkyl; C2-C4-alkyl which is substituted by xe2x80x94OH or xe2x80x94NR9R9xe2x80x2 wherein R9 and R9xe2x80x2 are each independently of another hydrogen or C1-C2-alkyl, or Y is a radical -C2-C4-alkylenexe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide; a radical xe2x80x94C(O)xe2x80x94NY1Y2, wherein Y1 and Y2 are each independently of the other hydrogen or C1-C4-alkyl which is unsubstituted or substituted by hydroxy, or Y1 and Y2 together with the adjacent N-atom form a heterocyclic 6-membered ring having no further heteroatom or having one further N- or O-atom; a radical xe2x80x94OY3, wherein Y3 is hydrogen, C1-C4-alkyl which is unsubstituted or substituted by xe2x80x94NH2 or xe2x80x94N(C1-C2-alkyl)2, or is a group xe2x80x94C(O)C1-C2-alkyl; or a 5- or 6-membered heteroaromatic or heteroaliphatic radical having one N-atom and in addition no further heteroatom or an additional N-, O- or S-heteroatom, or a 5 to 7-membered lactame.
A group of more preferred non-ionic substituents of B or Bxe2x80x2 comprises a radical xe2x80x94COOY, wherein Y is C1-C2-alkyl, C2-C3-alkyl, which is substituted by hydroxy, amino or N,N-di-C1-C2-alkylamino, or is a radical -C2-C4-alkylenexe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose; a radical xe2x80x94CO-NY1Y2, wherein Y1 and Y2 are each independently of the other hydrogen or C1-C2-alkyl which is unsubstituted or substituted by hydroxy, or Y1 and Y2 together with the adjacent N-atom form a N-C1-C2-alkylpiperazino or morpholino ring; or a heterocyclic radical selected from the group consisting of N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methylpyridin-5-yl, 2-, 3-oder 4-hydroxypyridinyl, N-s-caprolactamyl, N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl and 4xe2x80x94N-methylpiperazin-1-yl.
A particularly preferred group of non-ionic substituents of B or Bxe2x80x2 comprises the radicals xe2x80x94CONH2, xe2x80x94CON(CH3)2, xe2x80x94CONHxe2x80x94(CH2)2xe2x80x94OH, 
xe2x80x94COOxe2x80x94(CH2)2xe2x80x94N(CH3)2, and xe2x80x94COO(CH2)2-4xe2x80x94NHC(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose.
(ii) Anionic Substituents:
Preferred anionic substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is substituted by one or more substituents selected from the group consisting of xe2x80x94SO3H and xe2x80x94OPO3H2, for example xe2x80x94CH2xe2x80x94SO3H; phenyl which is substituted by xe2x80x94SO3H or sulfomethyl, for example o-, m- or p-sulfophenyl or o-, m- or p-sulfomethylphenyl; xe2x80x94COOH; a radical xe2x80x94COOY4, wherein Y4 is C2-C6-alkyl which is substituted by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2, or by a radical xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94Gxe2x80x2 wherein Gxe2x80x2 is the radical of lactobionic acid, hyaluronic acid or sialic acid, in particular C2-C4-alkyl which is substituted by xe2x80x94SO3H or xe2x80x94OSO3H; a radical xe2x80x94CONY5Y6 wherein Y5 is C1-C6-alkyl substituted by sulfo, in particular C2-C4-alkyl substituted by sulfo, and Y6 is hydrogen, for example the radical xe2x80x94C(O)xe2x80x94NHxe2x80x94C(CH3)2xe2x80x94CH2xe2x80x94SO3H; or xe2x80x94SO3H; or a suitable salt thereof. Particular preferred anionic substituents of B or Bxe2x80x2 are xe2x80x94COOH, xe2x80x94SO3H, o-, m- or p-sulfophenyl, o-, m- or p-sulfomethylphenyl or a radical xe2x80x94CONY5Y6 wherein Y5 iS C2-C4-alkyl substituted by sulfo, and Y6 is hydrogen, especially carboxy.
(iii) Cationic Substituents:
Preferred cationic substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is in each case substituted by xe2x80x94NR9R9xe2x80x2R9xe2x80x3+Anxe2x88x92; or a radical xe2x80x94C(O)OY7 wherein Y7 is C2-C6-alkyl, in particular C2-C4-alkyl, which is in each case substituted by xe2x80x94NR9R9xe2x80x2R9xe2x80x3+Anxe2x88x92 and is further unsubstituted or substituted by hydroxy. R9, R9xe2x80x2 and R9xe2x80x3 are each independently of another preferably hydrogen or C1-C4-alkyl, more preferably methyl or ethyl and particularly preferably methyl. Examples of suitable anions Anxe2x88x92 are Halxe2x88x92, wherein Hal is halogen, for example Brxe2x88x92, Fxe2x88x92, Jxe2x88x92or particularly Clxe2x88x92, furthermore HCO3xe2x88x92, CO32xe2x88x92, H2PO3xe2x88x92, HPO32xe2x88x92, PO33xe2x88x92, HSO4xe2x88x92, SO42xe2x88x92 or the radical of an organic acid such as OCOCH3xe2x88x92 and the like. A particularly preferred cationic substituent of B or Bxe2x80x2 is a radical xe2x80x94C(O)OY7 wherein Y7 is C2-C4-alkyl, which is substituted by xe2x80x94N(C1-C2-alkyl)3+Anxe2x88x92 and is further substituted by hydroxy, and Anxe2x88x92 is an anion, for example the radical xe2x80x94C(O)Oxe2x80x94CH2xe2x80x94 CH(OH)xe2x80x94CH2xe2x80x94N(CH3)3+Anxe2x88x92.
(iv) Zwitterionic Substituents -R3-Zw:
R3 is a preferably a carbonyl, ester or amide functional group and more preferably an ester group xe2x80x94C(O)xe2x80x94Oxe2x80x94.
Suitable anionic groups of the moiety Zw are for example xe2x80x94COOxe2x88x92, xe2x80x94SO3xe2x80x94, xe2x80x94OSO3xe2x80x94, xe2x80x94OPO3Hxe2x88x92 or bivalent xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94 or xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94Oxe2x80x94, preferably a group xe2x80x94COOxe2x80x94 or xe2x80x94SO3xe2x80x94 or a bivalent group xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94, and in particular a group xe2x80x94SO3xe2x80x94.
Suitable cationic groups of the moiety Zw are for example a group xe2x80x94NR9R9xe2x80x2R9xe2x80x3+or a bivalent group xe2x80x94NR9R9xe2x80x2+xe2x80x94, wherein R11R1xe2x80x2 and R9xe2x80x3 are as defined above, and are each independently of the other, preferably hydrogen or C1-C6-alkyl, preferably hydrogen or C1-C4-alkyl and most preferably each methyl or ethyl.
The moiety Zw is for example C2-C30-alkyl, preferably C2-C12-alkyl, and more preferably C3-C8-alkyl, which is in each case uninterrupted or interrupted by xe2x80x94Oxe2x80x94 and substituted or interrupted by one of the above-mentioned anionic and cationic groups each, and, in addition, is further unsubstituted or substituted by a radical xe2x80x94OY8, wherein Y8 is hydrogen or the acyl radical of a carboxylic acid.
Y8 is preferably hydrogen or the acyl radical of a higher fatty acid.
Zw is preferably C2-C12-alkyl and even more preferably C3-C8-alkyl which is substituted or interrupted by one of the above-mentioned anionic and cationic groups each, and in addition may be further substituted by a radical xe2x80x94OY8.
A preferred group of zwitter-ionic substituents -R3-Z corresponds to the formula
xe2x80x94C(O)Oxe2x80x94(alkxe2x80x2xe2x80x3)xe2x80x94N(R9)2+xe2x80x94(alkxe2x80x2)xe2x80x94Anxe2x88x92xe2x80x83xe2x80x83
or
xe2x80x94C(O)Oxe2x80x94(alkxe2x80x3)xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94(O)0-1xe2x80x94(alkxe2x80x2xe2x80x3)xe2x80x94N(R9)3+
wherein R9 is hydrogen or C1-C6-alkyl; Anxe2x88x92 is an anionic group xe2x80x94COOxe2x80x94, xe2x80x94SO3xe2x88x92, xe2x80x94OSO3xe2x88x92 or xe2x80x94OPO3Hxe2x88x92, preferably xe2x80x94COOxe2x88x92 or xe2x80x94SO3xe2x88x92 and most preferably xe2x80x94SO3xe2x88x92, alkxe2x80x2 is C1-C12-alkylene, (alkxe2x80x3) is C2-C24-alkylene which is unsubstituted or substituted by a radical xe2x80x94OY8, Y8 is hydrogen or the acyl radical of a carboxylic acid, and (alkxe2x80x2xe2x80x3) is C2-C8-alkylene.
(alkxe2x80x2) is preferably C2-C8-alkylene, more preferably C2-C6-alkylene and most preferably C2-C4-alkylene. (alkxe2x80x3) is preferably C2-C12-alkylene, more preferably C2-C6-alkylene and particularly preferably C2-C3-alkylene which is in each case unsubstituted or substituted by hydroxy or by a radical xe2x80x94OY8. (alkxe2x80x2xe2x80x3) is preferably C2-C4-alkylene and more preferably C2-C3-alkylene. R9 is hydrogen or C1-C4-alkyl, more preferably methyl or ethyl and particularly preferably methyl. A preferred zwitterionic substituent of B or Bxe2x80x2 is of formula
xe2x80x94C(O)Oxe2x80x94CH2xe2x80x94CH(OY8)xe2x80x94CH2xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94(CH2)2xe2x80x94N(CH3)3+, 
wherein Y8 is hydrogen or the acyl radical of a higher fatty acid.
In one embodiment of the invention one of B and Bxe2x80x2 may also be the radical of a hydrophobic comonomer which includes especially those customarily used in the manufacture of contact lenses. Suitable hydrophobic vinylic comonomers include, without the list being exhaustive acrylonitrile, methacrylonitrile, vinyl-C1-C18-alkanoates, C2-C18-alkenes, C2-C18-haloalkenes, styrene, C1-C6-alkylstyrene, C2-C10-perfluoroalkyl acrylates and methacrylates or correspondingly partially fluorinated acrylates and methacrylates, C3-C12-perfluoroalkyl-ethyl-thio-carbonylaminoethyl acrylates and methacrylates, acryloxy- and methacryloxy-alkylsiloxanes, N-vinylcarbazole and the like. Examples of suitable hydrophobic vinylic comonomers include acrylonitrile, methacrylonitrile, vinyl acetate, vinyl propionate, vinylbutyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, 1-butene, butadiene, vinyltoluene, perfluorohexylethylthiocarbonylaminoethyl methacrylate, trifluoroethyl methacrylate, hexafluoroisopropyl methacrylate, hexafluorobutyl methacrylate, tris-trimethylsilyloxy-silyl-propyl methacrylate, 3-methacryloxypropylpentamethyidisiloxane and bis(methacryloxypropyl)-tetramethyldisiloxane.
B denotes for example a radical of formula 
wherein R5 is hydrogen or C1-C4-alkyl, preferably hydrogen or methyl; R6 is a hydrophilic substituent, wherein the above given meanings and preferences apply; R7 is C1-C4-alkyl, phenyl or a radical xe2x80x94C(O)OY9, wherein Y9 is hydrogen or unsubstituted or hydroxy-substituted C1-C4-alkyl; and R8 is a radical xe2x80x94C(O)Y,xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY9xe2x80x2 wherein Y9xe2x80x2 independently has the meaning of Y9.
R7 is preferably C1-C2-alkyl, phenyl or a group xe2x80x94C(O)OY9. R8 is preferably a group xe2x80x94C(O)OY9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY9xe2x80x2 wherein Y9 and Y9xe2x80x2 are each independently of the other hydrogen, C1-C2-alkyl or hydroxy-C1-C2-alkyl. Particularly preferred xe2x80x94CHR7xe2x80x94CHR8xe2x80x94 units according to the invention are those wherein R7 is methyl or a group xe2x80x94C(O)OY9 and R8 is a group xe2x80x94C(O)OY9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY940  wherein Y9 and Y9xe2x80x2 are each hydrogen, C1-C2-alkyl or hydroxy-C1-C2-alkyl.
Bxe2x80x2 independently may have one of the meanings given above for B or is the radical of a hydrophobic comonomer, for example the radical of one of the above-given hydrophobic comonomers.
If (oligomer) is a telomer radical of formula (3a), the radical -(alk)xe2x80x94Sxe2x80x94[B]p-[Bxe2x80x2]q-Q preferably denotes a radical of formula 
even more preferably of the formula 
wherein for R5, R6, Q, p and q the above-given meanings and preferences apply, for R5xe2x80x2 independently the meanings and preferences given before for R5 apply, and for R6xe2x80x2 independently the meanings and preferences given before for R6 apply or R6xe2x80x2 is a hydrophobic substituent selected from the group consisting of hydrogen, xe2x80x94CN, C1-C18-alkanoyl, C1-C16-alkyl, C1-C16-haloalkyl, phenyl, C1-C6-alkylphenyl, C2-C10-perfluoroalkyloxycarbonyl or a corresponding partially fluorinated alkyloxycarbonyl radical, C3-C12-perfluoroalkyl-ethyl-thiocarbonylaminoethyloxycarbonyl, alkylsiloxyloxycarbonyl and carbazolyl
A preferred group of suitable hydrophilic macromers according to the invention comprises compounds of the above formula (1) wherein R is hydrogen or methyl, R1 is hydrogen, methyl or carboxyl, R1xe2x80x2 is hydrogen, A is a radical of the above formula (2a), (2b) or (2e), wherein n and m are each 0 or 1, X and X, are each independently of the other xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94, A1 is unsubstituted or hydroxy-substituted xe2x80x94O-C2-C8-alkylene or a radical xe2x80x94O-C2-C6-alkylenexe2x80x94NHxe2x80x94C(O)xe2x80x94, A2 is C1-C4-alkylene, phenylene or benzylene, (alk*) is C2-C4-alkylene, and (oligomer) denotes a radical of formula 
wherein (alk) is C2-C6-alkylene, Q is a monovalent group that is suitable to act as a polymerization chain-reaction terminator, p and q are each an integer of from 0 to 100 and the total of (p+q) is from 5 to 100, R5 and R5xe2x80x2 are each independently of the other hydrogen or methyl, and for R6 and R6xe2x80x2 each independently of the other the meanings and preferences given before apply. One particularly preferred embodiment of the above outlined hydrophilic macromers comprises those wherein q is 0, p is from 5 to 100, R5 is hydrogen or methyl, and R6 is a radical xe2x80x94CONH2, xe2x80x94CON(CH3)2, xe2x80x94CONHxe2x80x94(CH2)2xe2x80x94OH, 
xe2x80x94COOxe2x80x94(CH2)2xe2x80x94N(CH3)2, or xe2x80x94COO(CH2)2-4xe2x80x94NHC(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose. A further preferred embodiment of the above outlined hydrophilic macromers comprises those wherein p is from 4 to 99, q is from 1 to 96 wherein in the total of (p+q) is from 5 to 100, R5 and R5xe2x80x2 are each independently hydrogen or methyl, R6 is a radical xe2x80x94CONH2, xe2x80x94CON(CH3)2, xe2x80x94CONHxe2x80x94(CH2)2xe2x80x94OH, 
xe2x80x94COOxe2x80x94(CH2)2xe2x80x94N(CH3)2, or xe2x80x94COO(CH2)2-4xe2x80x94NHC(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose, and R6xe2x80x2 independently has the meaning of R1 or is carboxy, subject to the proviso that R6 and R6xe2x80x2 are different.
A more preferred group of suitable hydrophilic macromonomers according to the invention comprises compounds of formula 
wherein R is hydrogen or methyl, A1 is xe2x80x94Oxe2x80x94(CH2)2-4xe2x80x94, xe2x80x94Oxe2x80x94CH2xe2x80x94CH(OH)xe2x80x94CH2xe2x80x94 or a radical xe2x80x94Oxe2x80x94(CH2)2-4 xe2x80x94NHxe2x80x94C(O)xe2x80x94, X is xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94, (alk) is C2-C4-alkylene, Q is a monovalent group that is suitable to act as a polymerization chain-reaction terminator, p is an integer from 5 to 50, R5 is hydrogen or methyl, and for R6 the above given meanings and preferences apply.
A particularly preferred embodiment of the invention relates to hydrophilic macromonomers of the formula 
wherein for R, R5, R6, Q, (alk) and p the above-given meanings and preferences apply. A particularly preferred group of hydrophilic macromonomers are compounds of the above formula (1b) wherein R is hydrogen or methyl, (alk) is C2-C4-alkylene, R5 is hydrogen or methyl, p is an integer of 5 to 50, Q is as defined before, and for R6 the above given meanings and preferences apply.
If (oligomer) is a radical (ii) of formula (3b), Qxe2x80x2 in formula (3b) is for example C1-C12-alkyl, phenyl or benzyl, preferably C1-C2-alkyl or benzyl and in particular methyl. R29 is preferably unsubstituted or hydroxy-substituted C1-C4-alkyl and in particular methyl. u is preferably an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 10 to 50.
If (oligomer) is a radical of formula (3bxe2x80x2), the above given meanings and preferences apply for the variables X, R29 and u contained therein.
If (oligomer) denotes a radical (iv) of formula (3c),R2 and R2xe2x80x2 are each preferably ethyl or in particular methyl; v is preferably an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 10 to 50; Qxe2x80x3 is for example hydrogen; and Anxe2x88x92 is as defined before.
If (oligomer) denotes an oligopeptide radical (v) of formula (3d) or 3dxe2x80x2), R4 is for example hydrogen, methyl, hydroxymethyl, carboxymethyl, 1-hydroxyethyl, 2-carboxyethyl, isopropyl, n-, sec. or iso-butyl, 4-amino-n-butyl, benzyl, p-hydroxybenzyl, imidazolylmethyl, indolylmethyl or a radical xe2x80x94(CH2)3xe2x80x94NHxe2x80x94C(xe2x95x90NH)xe2x80x94NH2. t is preferably an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 10 to 50.
If (oligomer) denotes a polyoxyalkylene radical (vi) of formula (3e), R30 is preferably hydrogen or C1-C18-alkyl, more preferably hydrogen or C1-C12-alkyl, even more preferably hydrogen, methyl or ethyl, and particularly preferably hydrogen or methyl. (alk**) is preferably a C2-C3-alkylene radical. z is preferably 0. r and s are each independently preferably an integer from 0 to 100 wherein the total of (r+s) is 5 to 100. r and s are each independently more preferably an integer from 0 to 50 wherein the total of (r+s) is 8 to 50. In a particularly preferred embodiment of the polyoxyalkylene radicals (oligomer), r is an integer from 8 to 50 and particularly 9 to 25, and s is 0.
(oligomer) as the radical of an oligosaccharide (vii) may be, for example, a di- or polysaccharide including carbohydrate containing fragments from a biopolymer. Examples are the radical of a cyclodextrin, trehalose, cellobiose, maltotriose, maltohexaose, chitohexaose or a starch, hyaluronic acid, deacetylated hyaluronic acid, chitosan, agarose, chitin 50, amylose, glucan, heparin, xylan, pectin, galactan, glycosaminoglycan, mucin, dextran, aminated dextran, cellulose, hydroxyalkylcellulose or carboxyalkylcellulose oligomer, each of which with a molecular weight average weight of, for example, up to 25000, preferably up to 10000. Preferably the oligosaccharide according to (vii) is the radical of a cyclodextrin with a maximum of 8 sugar units.
In the above formulae (2a), (2b), (2c), (2d) and (2e), the left bond is in each case attached to the double bond whereas the right bond is linked to the oligomer. Formulae (3a), (3axe2x80x2) and (3e) are to be understood as a statistic description of the respective oligomeric radicals, that is to say, the orientation of the monomers and the sequence of the monomers (in case of copolymers) are not fixed in any way by said formulae. The arrangement of B and Bxe2x80x2 in formula (3a) or of the ethyleneoxide and propyleneoxide units in formula (3e) thus may be random or blockwise. Throughout the whole description, anions such as xe2x80x94COOH or xe2x80x94SO3H groups always include suitable salt forms, preferably biomedical or especially ophthalmically acceptable salts, in particular xe2x80x94COOxe2x88x92Ka+ and xe2x80x94SO3xe2x88x92Ka+ groups wherein Ka+ is a cation such as an alkali metal cation or an ammonium cation.
The weight average molecular weight of the macromonomers of the invention depends principally on the desired properties and is for example from 300 to 50000, preferably from 300 to 12000, more preferably from 300 to 8000, even more preferably 300 to 5000, and particularly preferably from 500 to 2000.
The macromonomers of formula (1) may be prepared by methods, for example as described in WO 99/57581.
The hydrophilic monomers and macromonomers may be applied to the initiator-modified bulk material surface and polymerized there according to processes known per se. For example, the bulk material is immersed in a solution of the monomer or macromonomer, or a layer of monomer or macromonomer is first of all deposited on the modified bulk material surface, for example, by dipping, spraying, spreading, knife coating, pouring, rolling, spin coating or vacuum vapor deposition. The polymerization of the macromonomer on the bulk material surface then may be initiated, for example, thermally by the action of heat or preferably by irradiation, particularly by UV radiation. Suitable light sources for the irradiation are known to the artisan and comprise for example mercury lamps, high pressure mercury lamps, xenon lamps, carbon arc lamps or sunlight. The time period of irradiation may depend for example on the desired properties of the resulting composite material but is usually in the range of up to 30 minutes, preferably from 10 secondes to 10 minutes, and particularly preferably from 0.5 to 5 minutes. The irradiation may be carried out under ambient conditions or in an atmosphere of an inert gas, for example nitrogen. After the polymerization, any non-covalently bonded polymers, oligomers or non-reacted monomer or macromonomers formed can be removed, for example by treatment with suitable solvents.
By means of the above-described coating process, hydrophilic monomers may be grafted to the bulk material surface with formation of a coating having for example a so-called brush-type structure.
Most important, the grafting of the macromonomers to the bulk material surface yields a coating having for example a so-called bottle brush-type structure (BBT) composed of tethered xe2x80x9chairyxe2x80x9d chains. Such BBT structures in one embodiment comprise a long hydrophilic or hydrophobic backbone which carries relatively densely packed comparatively short hydrophilic side chains (called primary bottle brushes). Another embodiment relates to secondary bottle brushes which are characterized in that the hydrophilic side chains themselves carry densely packed hydrophilic xe2x80x9csecondaryxe2x80x9d side chains. Polymeric coatings of said primary and secondary BBT structures to a certain extent mimic highly water-retaining structures occurring in the human body, for example in cartilage or mucosal tissue.
The coating thickness of the hydrophilic surface coating (b) depends principally on the desired properties. In case of macromonomers it can be used, for example, from 0.001 to 1000 xcexcm, preferably from 0.01 to 500 xcexcm, more preferably from 0.01 to 100 xcexcm, even more preferably from 0.05 to 50 xcexcm, especially preferably from 0.1 to 5 xcexcm and particularly preferably from 0.1 to 1 xcexcm. A particularly suitable range is from 0.2 to 0.6 xcexcm.
The complete coating of the bulk material according to the invention consists (a) of a polyionic material comprising one polyelectrolyte or preferably one or more bilayers of polyelectrolytes and (b) of an upper hydrophilic coating obtainable by grafting one or more hydrophilic monomers or 20 preferably macromonomers onto the surface, wherein the latter makes up at least 50%, preferably from 75 to 98% and particularly preferably from 80 to 95% of the total thickness of the fully hydrated coating.
A further embodiment of the invention is a biomedical device, e.g. an ophthalmic device, preferably a contact lens including both hard and particularly soft contact lenses, an intraocular lens or artificial cornea, comprising a composite material according to the invention and particular a composite material comprising a macromonomer-based surface coating. The inventive materials are further useful for example as wound healing dressings, eye bandages, materials for the sustained release of an active compound such as a drug delivery patch, moldings that can be used in surgery, such as heart valves, vascular grafts, catheters, artificial organs, encapsulated biologic implants, e.g. pancreatic islets, materials for prostheses such as bone substitutes, or moldings for diagnostics, membranes or biomedical instruments or apparatus.
The biomedical devices, e.g. ophthalmic devices according to the invention have a variety of unexpected advantages over those of the prior art which make those devices very suitable for practical purposes, e.g. as contact lens for extended wear or intraocular lens. For example, they do have a high surface wettability which can be demonstrated by their contact angles, their water retention ability and their water-film break up time or tear film break up time (TBUT).
The TBUT plays an particularly important role in the field of ophthalmic devices such as contact lenses. Thus the facile movement of an eyelid over a contact lens has proven important for the comfort of the wearer; this sliding motion is facilitated by the presence of a continuous layer of tear fluid on the contact lens, a layer which lubricates the tissue/lens interface. However, clinical tests have shown that currently available contact lenses partially dry out between blinks, thus increasing friction between eyelid and the lens. The increased friction results in soreness of the eyes and reduced movement of the contact lenses. Taking into account the average time period between two blinks of an eye it follows that a wettable and biocompatible contact lens should hold a continuous layer of tear fluid for more than 10 seconds and preferably for more than 15 seconds. Whereas current biomedical materials in general have TBUTs of well below 10 seconds and thus do not reach this target, the composite materials of the present invention have TBUTs of  greater than 10 seconds and especially  greater than 15 seconds. In addition, the TBUT of commercial contact lenses may be improved considerably by applying a surface coating according to the invention. For example, the TBUT of commercial contact lenses such as Focus Dailies(trademark), Focus New Vues(copyright) or Lotrafilcon A lenses, may be increased by more than 50% or, according to a particularly preferred embodiment, by xe2x89xa7100% by applying a surface coating according to the invention. On the base curve of a contact lens, the pronounced lubricity of the coating facilitates the on-eye lens movement which is essential for extended wear of contact lenses. Moreover, the composite materials of the invention provide additional effects being essential for lenses for extended wear, such as an increased thickness of the pre-lens tear film and of the topical lipid layer of the tear film which each contributes substantially to low microbial adhesion and resistance to deposit formation. Due to the extremely soft and lubricious character of the novel surface coatings, biomedical articles such as in particular contact lenses made from an inventive composite material show a superior wearing comfort including improvements with respect to late day dryness, long term (overnight) wear and acute vision on awake. The novel surface coatings moreover interact in a reversible manner with occular mucus which contributes to the improved wearing comfort.
In addition, biomedical devices, e.g. ophthalmic devices such as contact lenses, comprising a composite material of the invention have a very pronounced biocompatibility combined with good mechanical properties. For example, the devices are blood compatible and have a good tissue integration. In addition, there are generally no adverse eye effects observed, while the adsorption of proteins or lipids is low, also the salt deposit formation is lower than with conventional contact lenses. Generally, there is low fouling, low microbial adhesion and low bioerosion while good mechanical properties can be for example found in a low friction coefficient and low abrasion properties. Moreover, the dimensional stability of the composite materials of the invention is excellent. In addition, the attachment of a hydrophilic surface coating at a given bulk material according to the invention does not affect its visual transparency.
In summary, the ophthalmic devices according to the invention, such as intraocular lenses and artificial cornea or particularly contact lenses, provide a combination of low spoilation with respect to cell debris, cosmetics, tear components, lipids, proteins, salts, dust or dirt, solvent vapors or chemicals, with a high comfort for the patient wearing such opthalmic devices in view of the soft hydrogel surface which for example provides a very good on-eye movement of the ohthalmic device.
Biomedical devices such as renal dialysis membranes, blood storage bags, pacemaker leads or vascular grafts made of the composite materials of the invention resist fouling by proteins by virtue of the continuous layer of bound water, thus reducing the rate and extent of thrombosis.
Blood-contacting devices fabricated according to the present invention are therefore haemocompatible and biocompatible.
In the examples, if not indicated otherwise, amounts are amounts by weight, temperatures are given in degrees Celsius. Tear break-up time values in general relate to the pre-lens tear film non-invasive break-up time (PLTF-NIBUT) that is determined following the procedure published by M. Guillon et al., Ophthal. Physiol. Opt. 9, 355-359 (1989) or M. Guillon et al., Optometry and Vision Science 74, 273-279 (1997). Average advancing and receding water contact angles of coated and non-coated lenses are determined with the dynamic Wilhelmy method using a Krxc3xcss K-12 instrument (Krxc3xcss GmbH, Hamburg, Germany). Wetting force on the solid is measured as the solid is immersed in or withdrawn from a liquid of known surface tension.